Polymorphisms in human leukocyte antigens, human platelet antigens, and cytokine genes in hantavirus cardiopulmonary syndrome patients from Ribeirão Preto, Brazil

Abstract

Hantavirus cardiopulmonary syndrome is a severe human disease associated with hantavirus infection. The clinical course of illness varies greatly among individuals, possibly due to viral and immunological elements and the influence of host genetic factors on clinical outcome. As the magnitude of immune activation has been associated with disease severity, polymorphisms in genes involved in the immune response that may affect the development of this syndrome were investigated. Polymorphisms in the TGF-β, IL-10, IL-6, and IFN-γ genes, human leukocyte antigens (HLA), and human platelet alloantigens (HPA) genes were investigated in 122 patients with Araraquara virus infection from Ribeirão Preto, Brazil. Patients were divided into two groups: hantavirus cardiopulmonary syndrome (HCPS group; n = 26) and hantavirus seropositive only (n = 96). The frequencies of HLA alleles, cytokines and platelet antigen genotypes were evaluated in both groups and compared to a control group. The data demonstrated no significant influence of the HLA alleles, HPA, IL-6, and IL-10 genotypes on susceptibility to hantavirus infection. However, the hantavirus seropositive group presented a significantly higher frequency of a polymorphism associated with a high IFN-γ production than the HCPS group. In addition, a genotype associated with high TGF-β production was found more frequently in individuals infected with hantavirus than in the control group. This phenotype was associated with a less intense thrombocytopenia in the HCPS group and may be protective against the most severe form of hantavirus disease. More studies are required to quantify further the influence of the high TGF-β producer phenotype on the outcome of hantavirus infection.

Viral Hemorrhagic Fevers Other than Ebola and Lassa

“…96,102 Host factor such as HLA B*35 have been associated to an increased risk for severe HCPS outcomes. 103 During convalescence in patients with severe HCPS viral genome can be detected up to 90 days after the onset of clinical symptoms. 96 Hantaviruses can cause two zoonotic diseases in humans: HFRS or HCPS.…”

Hantavirus Cardiopulmonary Syndrome Due to Imported Andes Hantavirus Infection in Switzerland: A Multidisciplinary Challenge, Two Cases and a Literature Review

“…In this phase, the disease can rapidly progress to multiorgan failure, and death may occur within 24 hours [ 25 ]. Disease pathology, which is characterized by microvascular leakage, is mainly attributed to host immune response, illustrated by the fact that infection of endothelial cells does not lead to cytopathology [ 26 , 27 ]. Viral load does not appear to predict the severity of clinical presentation [ 3 ].…”

Deletions in Genes Participating in Innate Immune Response Modify the Clinical Course of Andes Orthohantavirus Infection

“…Several studies have suggested that host genetic constitution may influence the clinical outcome of hantavirus infection, resulting in mild or severe disease [16,17,18,19,20,21]. In HCPS patients, HLA-B*08 and HLA-DRB1*15 alleles were associated with disease severity, as well as polymorphisms in the IL28B gene [17,22].…”